Новый подход к получению оксадиазецинонов из N-замещённых аминоэтанолов и 1,4оксазепинонов

Данная работа посвящена расширению методологии синтеза циклов среднего размера (ЦСР) через реакцию раскрытия гидратированного имидазолинового фрагмента (HIRE) за счет использования в качестве прекурсоров N-замещённых аминоэтанолов и [1,4]оксазепинонов. Подобные соединения представляют огромный интерес в связи с тем, что молекулы, содержащие ЦСР, находят широкое применение в качестве биологически активных веществ.
В ходе проделанной работы была разработана методика синтеза [1,4]оксазепинов, конденсированных с кватернизированным имидазолиновым фрагментом, которые в дальнейшем подвергались гидролитическому раскрытию при действии водного раствора K2CO3, приводя в большинстве случаев к целевым [1,4,7]оксадиазецинонам. Кроме того, впервые было обнаружено альтернативное направление раскрытия гидратированного имидазолина, приводящее к образованию N-аминоэтильных производных. Также было показано, что N-аминоэтильные производные диареноксазепинонов могут быть перегруппированы в циклы среднего размера в более жёстких условиях.
Стоит отметить, что данный протокол применим и для формирования 11-членных лактамов, которые могут существовать в двух стабильных изомерных формах.

Перечень условных обозначений …………………………………………………………………………..4

Введение …………………………………………………………………………………………………………………6

1. Обзор литературы …………………………………………………………………………………………….10

1.1 Методы получения ди(гетеро)ареноксазепинонов …………………………………………..10

1.1.1 Получение оксазепинонов путём формирования связи C(=O)-N ………………..10

1.1.2 Получение оксазепинонов путём образования связи C-O …………………………..11

1.1.3 Получение оксазепинонов путём образования связей C-O и C(=O)-N ……….12

1.1.4 Получение оксазепинонов путём образования связей C-O и C-Nамид …………12

1.1.5 Получение оксазепинонов путём формирования связей C(=O)-N и C-Nамид .14

1.1.6 Получение оксазепинонов путём формирования связей С(=O)-N и C-C(=O)
………………………………………………………………………………………………………………………..15

1.1.7 Получение оксазепинонов путём образования связей C(=O)-N, C-O и C-
C(=O) ………………………………………………………………………………………………………………15

1.2 Методы гидролитического раскрытия имидазолинового фрагмента,
конденсированного с циклической системой ………………………………………………………16

1.2.1 Гидролитическое раскрытие в системах с циклами малого размера ………….16

1.2.2 Гидролитическое раскрытие в системах с циклами нормального размера ….17

1.2.3 Гидролитическое раскрытие в системах с циклами среднего размера ……….20

1.2.4 Гидролитическое раскрытие в системах с макроциклами …………………………21

1.3 Реакции трансамидирования …………………………………………………………………………..21

2. Обсуждение результатов …………………………………………………………………………………..27

2.1 Получение оксазепинонов ……………………………………………………………………………..27

2.2 Получение N-замещённых алифатических аминоспиртов ………………………………30

2.3 Формирование производных 1,4,7-оксадиазецинонов из оксазепинонов и N-
замещенных аминоэтанолов по реакции HIRE ……………………………………………………..31
2.4 Формирование производных [1]окса[4,8]диазациклоундецинонов из
оксазепинонов и N-замещенных аминопропанолов по реакции HIRE ……………………39

3. Экспериментальная часть ………………………………………………………………………………..47

Выводы …………………………………………………………………………………………………………………65

Благодарности ………………………………………………………………………………………………………66

Список цитированной литературы ……………………………………………………………………..67

Приложение ………………………………………………………………………………………………………….73

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